ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.100446dup (p.Glu33483fs)

dbSNP: rs878854281
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234691 SCV000286383 pathogenic Dilated cardiomyopathy 1G 2017-01-24 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 357 of the TTN mRNA (c.100446dupA), causing a frameshift at codon 33483. This creates a premature translational stop signal (p.Glu33483Argfs*8) and is expected to result in an absent or disrupted protein product. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are significantly overrepresented in patients with dilated cardiomyopathy and are considered to be likely pathogenic for the disease (PMID: 25589632). This variant has been shown to segregate with dilated cardiomyopathy in a family tested at Invitae. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000488121 SCV000575270 likely pathogenic not provided 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001388567 SCV001589604 pathogenic Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2023-04-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). ClinVar contains an entry for this variant (Variation ID: 238688). This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu33483Argfs*8) in the TTN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein.

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